Ingrid R. Olson - US grants

DESCRIPTION (provided by applicant): Foreknowledge about what will happen, when it will happen, and where it will happen, can help an organism find food and avoid predators. Preparatory responses use this foreknowledge to ready sensory and motor systems. Recent findings from neurophysiology and neuroimaging suggest that portions of the posterior parietal cortex (PPC) may function as a preparatory region. For instance, neurons in the monkey PPC region respond as though signaling the re-emergence of a briefly occluded moving target. Other studies have shown that cells in the PPC begin to fire seconds before a monkey looks a certain direction or reaches a certain direction. However, the functionality of the PPC is disputed because many studies have reported that various other tasks - attention, working memory, shape processing - also depend on the PPC. In this grant we advance the hypothesis that the PPC is importantly involved in linking sensory and motor signals in preparation to act. In Aim 1 we address the relationship of preparatory responses to working memory. In Aim 2 the relationship of sensory expectations to motor expectations is examined to gain some understanding of both the generality and specificity of preparatory processing. Last of all, in Aim 3 we do a finer grained analysis of preparatory processing by asking whether activity in the IPS is sensitive to the value of a preparatory cue. These questions will be addressed through functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and behavioral experimentation.

? DESCRIPTION (provided by applicant): Humans are an intrinsically social species. Our advanced socio-emotional skills are thought to underpin our tremendous cultural advances as well as the evolution of language. Our superior social skills are underpinned by an increased proficiency in the identification of, and access to knowledge about other people. Social knowledge is supported by increased specialization in a number of cortical regions involved in face processing as well as higher-level regions involved in linking biographical knowledge as well as motivational value to specific faces. In this renewal of our prior R01, we propose to extend our work on the anterior temporal lobes (ATLs) to examine a more specialized circuit for person knowledge. This circuit involves a region in the ventral ATL (vATL) that when damaged, leads to person memory deficits. The vATL face patch appears to serve as an interface between face perception and person memory, linking perceptual representations of distinct identities with abstract person knowledge. However this region does not act alone. We will use multivariate fMRI as well as structural and functional connectivity analyses to examine the flexible interaction of this region with perceptual systems, episodic memory systems, and hedonic valuation systems. Success in this project will significantly advance our understanding of the basic neural mechanisms that contribute to high-level social processing and will have important clinical implications for disorders that have core social knowledge deficits such as autism spectrum disorder and schizophrenia.

Project Summary Accurate memory for a specific past event is a cornerstone of human cognition, allowing for the use of past experiences to optimally guide future behaviors. Episodic memory underlies the ability for children make well-considered decisions, interact with others in a socially appropriate and develop the life narrative that gives coherence to their self-concepts over time. Thus, it is imperative that we understand in detail how memory develops in childhood, and how environmental factors may alter the typical developmental trajectories of episodic memory. There has been much work on age-related differences in encoding and retrieval, and a range of variables have been identified that contribute to age-related improvements in memory function, e.g., poor use of encoding strategies. In contrast, how a critical phase of memory processing ? memory consolidation ? develops in childhood has received little attention. This lack exposes a crucial scientific gap in our understanding of memory development. In this proposal we examine a key mechanism of memory consolidation called ?replay? in the rodent literature, post-encoding reactivation, in the human literature, and how it develops in childhood. This phenomenon was first observed in rodents that were trained to navigate a maze while hippocampal place cell activity was recorded. Later, during post-learning sleep, the neuronal firing patterns within hippocampal place cells recapitulated the firing patterns present during the awake learning phase. Replay can also be observed during periods of quiet wakefulness. This fact has been leveraged in the human literature by examining fMRI scans from rest periods that follow periods of learning. Drawing on predictions derived from computational models of memory, we ask whether poorer memory in children is partly accounted for by perturbed post-encoding reactivation mechanisms. To address this question, both children and young adults will undergo an fMRI scan while encoding associations between items and locations, interleaved with rest scans. We predict that factors that compromise the integrity of the hippocampus, or the ability of the hippocampus to rapidly communicate with neocortex, will alter reactivation and memory performance. Besides examining the key factor of age, children from high and low socioeconomic status (SES) backgrounds will be tested. Low SES/high stress environments have been associated with poorer memory and smaller hippocampi. In addition, we will measure structural connectivity between the hippocampus and cortical regions using cutting-edge imaging techniques. Thus we will examine whether age, environmental factors, and individual differences in structural connectivity alter a key mechanism underlying memory consolidation, and how this set of variables affects the behavioral expression of memory.

Project Summary Accurate memory for a specific past event is a cornerstone of human cognition, allowing for the use of past experiences to optimally guide future behaviors. Episodic memory underlies the ability for children make well-considered decisions, interact with others in a socially appropriate and develop the life narrative that gives coherence to their self-concepts over time. Thus, it is imperative that we understand in detail how memory develops in childhood, and how environmental factors may alter the typical developmental trajectories of episodic memory. There has been much work on age-related differences in encoding and retrieval, and a range of variables have been identified that contribute to age-related improvements in memory function, e.g., poor use of encoding strategies. In contrast, how a critical phase of memory processing ? memory consolidation ? develops in childhood has received little attention. This lack exposes a crucial scientific gap in our understanding of memory development. In this proposal we examine a key mechanism of memory consolidation called ?replay? in the rodent literature, post-encoding reactivation, in the human literature, and how it develops in childhood. This phenomenon was first observed in rodents that were trained to navigate a maze while hippocampal place cell activity was recorded. Later, during post-learning sleep, the neuronal firing patterns within hippocampal place cells recapitulated the firing patterns present during the awake learning phase. Replay can also be observed during periods of quiet wakefulness. This fact has been leveraged in the human literature by examining fMRI scans from rest periods that follow periods of learning. Drawing on predictions derived from computational models of memory, we ask whether poorer memory in children is partly accounted for by perturbed post-encoding reactivation mechanisms. To address this question, both children and young adults will undergo an fMRI scan while encoding associations between items and locations, interleaved with rest scans. We predict that factors that compromise the integrity of the hippocampus, or the ability of the hippocampus to rapidly communicate with neocortex, will alter reactivation and memory performance. Besides examining the key factor of age, children from high and low socioeconomic status (SES) backgrounds will be tested. Low SES/high stress environments have been associated with poorer memory and smaller hippocampi. In addition, we will measure structural connectivity between the hippocampus and cortical regions using cutting-edge imaging techniques. Thus we will examine whether age, environmental factors, and individual differences in structural connectivity alter a key mechanism underlying memory consolidation, and how this set of variables affects the behavioral expression of memory.

Project Summary Episodic memory binds together the people, objects, and locations that make up the specific events of our lives, forming multi-element traces of experiences that can guide ongoing behavior, help imagine the future, and enhance well-being. Episodic memory is poor in young children, a phenomenon called childhood amnesia. It gradually improves over the preschool years, with further refinement in elementary school. Understanding this developmental change requires linking research at three levels of analysis: (1) dissecting component processes of episodic memory in controlled laboratory tasks; (2) assessing underlying neural changes; and (3) evaluating children's naturalistic behaviors, both in the memory domain (self-related episodic memory and memory conversations with adults) and more generally. We propose a longitudinal study of children from 4 to 6 years and from 6 to 8 years, i.e., across the offset of childhood amnesia, with rich evaluation of all three components at three points in time. This multi-componential study across levels of analysis will be the first of its kind. Relational binding of multiple elements within an event may be conceptualized as the formation of coherent multi-element episodes that allows for pattern completion, i.e., the elicitation of all components of the experience from a subset. Another process involved in episodic memory is pattern separation. The Complementary Learning Systems (CLS) model, as well as earlier mathematical models of the hippocampus and later refinements of CLS, proposes that the hippocampus (HC) is specialized for the rapid and automatic acquisition of information that is then orthogonalized to reduce potential interference among similar memories. We will test children's abilities to retrieve all elements of an episode via pattern completion and children's abilities to discriminate between overlapping episodes containing similar people, objects or spatial contexts via pattern separation. In addition, a rich research tradition explores self-related episodic memories and their retention over time, as well as their linkage to environmental support. We will link findings regarding children's naturalistic behavior to laboratory measures of episodic memory and to neural development. These relations are likely bi-directional in causality, and hence longitudinal evaluation is essential. The behavioral work will be complemented by work at the neural level. Both pattern completion and pattern separation depend on the HC and are associated with maturation of its subfields, and the maturation of connectivity between the HC and cortical control structures. Using high-definition MRI and cutting-edge diffusion imaging parameters, we will test the hypothesis that specific hippocampal subfields perform pattern completion (CA3) and separation (dentate gyrus). In addition, we will test whether white matter pathways, both within the HC (e.g., perforant path) as well as long-range tracts linking the HC to neocortical areas, relate to pattern completion/separation behavioral performance.

Project Summary Episodic memory binds together the people, objects, and locations that make up the specific events of our lives, forming multi-element traces of experiences that can guide ongoing behavior, help imagine the future, and enhance well-being. Episodic memory is poor in young children, a phenomenon called childhood amnesia. It gradually improves over the preschool years, with further refinement in elementary school. Understanding this developmental change requires linking research at three levels of analysis: (1) dissecting component processes of episodic memory in controlled laboratory tasks; (2) assessing underlying neural changes; and (3) evaluating children's naturalistic behaviors, both in the memory domain (self-related episodic memory and memory conversations with adults) and more generally. We propose a longitudinal study of children from 4 to 6 years and from 6 to 8 years, i.e., across the offset of childhood amnesia, with rich evaluation of all three components at three points in time. This multi-componential study across levels of analysis will be the first of its kind. Relational binding of multiple elements within an event may be conceptualized as the formation of coherent multi-element episodes that allows for pattern completion, i.e., the elicitation of all components of the experience from a subset. Another process involved in episodic memory is pattern separation. The Complementary Learning Systems (CLS) model, as well as earlier mathematical models of the hippocampus and later refinements of CLS, proposes that the hippocampus (HC) is specialized for the rapid and automatic acquisition of information that is then orthogonalized to reduce potential interference among similar memories. We will test children's abilities to retrieve all elements of an episode via pattern completion and children's abilities to discriminate between overlapping episodes containing similar people, objects or spatial contexts via pattern separation. In addition, a rich research tradition explores self-related episodic memories and their retention over time, as well as their linkage to environmental support. We will link findings regarding children's naturalistic behavior to laboratory measures of episodic memory and to neural development. These relations are likely bi-directional in causality, and hence longitudinal evaluation is essential. The behavioral work will be complemented by work at the neural level. Both pattern completion and pattern separation depend on the HC and are associated with maturation of its subfields, and the maturation of connectivity between the HC and cortical control structures. Using high-definition MRI and cutting-edge diffusion imaging parameters, we will test the hypothesis that specific hippocampal subfields perform pattern completion (CA3) and separation (dentate gyrus). In addition, we will test whether white matter pathways, both within the HC (e.g., perforant path) as well as long-range tracts linking the HC to neocortical areas, relate to pattern completion/separation behavioral performance.

PROJECT SUMMARY/ABSTRACT This application is a five-year plan to create a Mid-Atlantic Neuroscience Diversity Scholars (MiNDS) program to bolster the number of underrepresented minority (URM) students within the neuroscience academic pipeline and build a foundation for URM students to succeed in graduate school and beyond. The program will comprise a partnership between Temple University, Lincoln University, and University of Maryland ? all institutions with a strong commitment to educating URM students and a commitment to building neuroscience research. Our program will recruit 9 scholars per year and provide them with the tools necessary for persistence within academia focusing on 6 elements: (1) integrated research experiences during the academic year, (2) immersive summer research experiences at R1 universities, (3) opportunities to build presentation skills at local and national meetings, (4) coursework to build technical excellence in Neuroscience, (5) professional skills training and mentoring to facilitate the transition to Neuroscience graduate programs, and (6) outreach activities to foster community and build teaching skills. Scholars will participate in a 2-year bridge program during their last two years of undergraduate study. Students in our MiNDS program will be provided with a comprehensive research training experience, including financial support for academic year research at their home institution, travel funds to present their research both at the MiNDS retreat, and at the Society for Neuroscience annual meeting, and stipend to engage in summer research at T32 funded institutions, Temple University or University of Maryland Baltimore, within the labs of faculty with exceptional behavioral or cognitive neuroscience research programs and extensive undergraduate mentoring experience. The program will provide MiNDS with a foundation of coursework and professional development to set the stage for the next step of their neuroscience research career. This will include one-on-one faculty mentoring in oral presentation skills, scientific writing, graduate school application review, and interview preparation. Additionally, students in MiNDS will be paired with senior graduate student mentors during this summer experience to gain further insight into the transition to PhD programs. The final core goal of the MiNDS initiative is to foster professional development of both students and mentors through community outreach. MiND scholars will team with faculty to develop outreach activities to engage 5th and 6th graders in neuroscience. These initiatives will position MiND scholars for success in a career in academic neuroscience research. To sure this success, the MiNDS program will be evaluated by our Advisory Board annually.